We read with interest the recent article by Toledo et al. [1].
In their study, the authors found that mRNA levels for SIRT1 were
increased in muscle from tumor-bearing rats and that
SIRT3 mRNA levels were unchanged. In the discussion of the
results, the authors stated that the observation of unchanged SIRT3
“is in contrast with that of Alamdari et al. [39] showing an
upregulation of SIRT3 in skeletal muscle during sepsis”. This
was a surprising statement since we did not examine or
report on SIRT3 expression in our study [2].
We did examine the effects of sepsis on the mRNA levels for the histone
deacetylases HDAC3 and 6 and nuclear protein levels
for the same HDACs as well as for SIRT1. Importantly,
protein levels for HDAC6 and SIRT1 were decreased (not increased) and
muscle HDAC activity was reduced during sepsis.

We think the misquotation of our work in the article by Toledo et al. [1]
was unfortunate, not only because it was erroneous but also because it
suggests that the expression of a histone deacetylase
(SIRT3) may be increased during sepsis, implying increased
deacetylase activity and reduced levels of acetylated cellular
proteins. This is opposite to the conclusions in our paper [2] and in other recent reports from our laboratory [3–7]
in which we found evidence that muscle wasting caused by sepsis and
glucocorticoids is associated with, and probably at
least in part regulated by increased acetylation of cellular
proteins. These conclusions were also supported by experiments
in which treatment of cultured muscle cells [4] or rats in vivo [2]
with histone deacetylase inhibitor increased the expression of
atrogin-1 and stimulated protein breakdown. In more recent
experiments, we found evidence for a role of reduced (not
increased) SIRT1 expression and activity in glucocorticoid-induced
muscle wasting [7]. It was surprising to see that SIRT1 mRNA levels were increased in muscle from tumor-bearing rats in the study by Toledo
et al. [1]. It would have been interesting to have information about SIRT1 protein levels and HDAC activity in the same muscles.

Sincerely,

Nima Alamdari,

Per-Olof Hasselgren

Acknowledgments The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the Journal
of Cachexia, Sarcopenia and Muscle [8].

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